Abstract

Objective: To investigate the potential protective effects of amitriptyline and fluoxetine in a catecholamine cell model.

Methods: Cultured rat pheochromocytoma (PC12) cells were pretreated with amitriptyline or fluoxetine for 24 or 48 hours and were then subjected to neurotoxic insult (200 μmol/L hydrogen peroxide). Cell viability was determined by measurement of the reduction product of 3-[4,5-dimethylthiazol-2-yl]-2,5-iphenyltetrazolium bromide (MTT). The enzyme activity of superoxide dismutase (SOD) was determined by a
commercial SOD assay kit.

Results: The decrease in cell viability induced by hydrogen peroxide was attenuated in PC12 cells pretreated with 100 μmol/L amitriptyline for 24 hours or with 50 μmol/L amitriptyline or 50 μmol/L fluoxetine for 48 hours. Pretreatment with either amitriptyline or fluoxetine was associated with increased SOD activity in PC12 cells. Inhibition of SOD activity with diethyldithiocarbamic acid reduced the cytoprotective action of fluoxetine.

Conclusions: These data suggest that the neuroprotective actions of some antidepressants include the upregulation of SOD activity.

Acknowledgements: We thank Dr. A.V. Juorio for his valuable discussions. This work was supported by the Canadian Psychiatric Research Foundation and the Saskatchewan Health Research Foundation.

Competing interests: None declared.

Contributors: The study was conceived by Drs. Kolla and Wei, and all authors participated in the experimental design. Drs. Kolla and Wei were responsible for data acquisition. All authors participated in data interpretation and drafting the article, and gave final approval for the version to be published.